Accelerated brain aging in major depressive disorder and antidepressant treatment response: A CAN-BIND report

Affiliations

¹ Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada.
² Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
³ Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁴ Rotman Research Institute, Baycrest, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, ON, Canada.
⁵ Rotman Research Institute, Baycrest, Toronto, ON, Canada.
⁶ Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
⁷ Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
⁸ Departments of Psychiatry and Psychology, Queen's University, and Providence Care, Kingston, ON, Canada.
⁹ Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
¹⁰ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Mental Health, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada; Centre for Depression and Suicide Studies, and Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
¹¹ Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada. Electronic address: freybn@mcmaster.ca.

PMID: 34710675
PMCID: PMC8556529
DOI: 10.1016/j.nicl.2021.102864

Accelerated brain aging in major depressive disorder and antidepressant treatment response: A CAN-BIND report

Pedro L Ballester et al. Neuroimage Clin. 2021.

. 2021:32:102864.

doi: 10.1016/j.nicl.2021.102864. Epub 2021 Oct 23.

Authors

Affiliations

¹ Neuroscience Graduate Program, McMaster University, Hamilton, ON, Canada.
² Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
³ Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁴ Rotman Research Institute, Baycrest, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, ON, Canada.
⁵ Rotman Research Institute, Baycrest, Toronto, ON, Canada.
⁶ Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
⁷ Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
⁸ Departments of Psychiatry and Psychology, Queen's University, and Providence Care, Kingston, ON, Canada.
⁹ Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
¹⁰ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Mental Health, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada; Centre for Depression and Suicide Studies, and Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
¹¹ Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada. Electronic address: freybn@mcmaster.ca.

PMID: 34710675
PMCID: PMC8556529
DOI: 10.1016/j.nicl.2021.102864

Abstract

Objectives: Previous studies suggest that major depressive disorder (MDD) may be associated with volumetric indications of accelerated brain aging. This study investigated neuroanatomical signs of accelerated aging in MDD and evaluated whether a brain age gap is associated with antidepressant response.

Methods: Individuals in a major depressive episode received escitalopram treatment (10-20 mg/d) for 8 weeks. Depression severity was assessed at baseline and at weeks 8 and 16 using the Montgomery-Asberg Depression Rating Scale (MADRS). Response to treatment was characterized by a significant reduction in the MADRS (≥50%). Nonresponders received adjunctive aripiprazole treatment (2-10 mg/d) for a further 8 weeks. The brain-predicted age difference (brain-PAD) at baseline was determined using machine learning methods trained on 3377 healthy individuals from seven publicly available datasets. The model used features from all brain regions extracted from structural magnetic resonance imaging data.

Results: Brain-PAD was significantly higher in older MDD participants compared to younger MDD participants [t(147.35) = -2.35, p < 0.03]. BMI was significantly associated with brain-PAD in the MDD group [r(155) = 0.19, p < 0.03]. Response to treatment was not significantly associated with brain-PAD.

Conclusion: We found an elevated brain age gap in older individuals with MDD. Brain-PAD was not associated with overall treatment response to escitalopram monotherapy or escitalopram plus adjunctive aripiprazole.

Keywords: Brain age; Machine learning; Major depressive disorder; Treatment response.

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Conflict of interest statement

RM has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE, Lallemand, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI and OMHF.

RWL has received honoraria or research funds from Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Michael Smith Foundation for Health Research, MITACS, Myriad Neuroscience, Ontario Brain Institute, Otsuka, Pfizer, Unity Health, and VGH-UBCH Foundation.

VHT has received honoraria from Novonordisk.

PLB, JS, SH, NN, and BNF, SS, SA, LM, RS, DJM, SHK have no conflicts of interest to report.

Figures

**Fig. 1**
Associations between age-corrected brain-PAD and chronological age for healthy control and treatment groups. On the left, chronological age is significantly associated with brain-PAD in the treatment group. Similarly, on the right, chronological age² was significantly associated with brain-PAD in the treatment group. Outliers have been removed from this analysis.

See this image and copyright information in PMC

References

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Accelerated brain aging in major depressive disorder and antidepressant treatment response: A CAN-BIND report

Affiliations

Accelerated brain aging in major depressive disorder and antidepressant treatment response: A CAN-BIND report

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

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Miscellaneous